Controlled production of recombinant polypeptides is useful in the fields of research, diagnostics and therapeutics. For example, purified recombinant proteins can be used as therapeutics, for screening, for lead optimization and for target validation. Typical expression systems are characterized by a host cell line comprising an expression vector containing a heterologous promoter operatively linked to a cDNA encoding a gene product of interest. See, for example, U.S. Pat. Nos. 5,168,062 and 5,385,839. Additional methods for protein production involve integration of promoters or other regulatory sequences into a chromosome adjacent to a gene whose expression is to be regulated. See, e.g., U.S. Pat. Nos. 5,272,071; 5,641,670; 5,733,761; 5,968,502 and 6,361,972.
Expression systems which yield levels of protein that are higher than those obtained using presently available systems are desirable.